2021 AACR | Selpercatinib in the treatment of RET fusion-positive solid tumors with an ORR of 47%

The 2021 American Association for Cancer Research (AACR) Annual Meeting will be held online on April 10-15 and May 17-21, 2021.

This annual conference covers the most cutting-edge research results in the field of tumor research.

In the special session of the clinical research plenary session, the efficacy and safety results of selpercatinib in RET fusion-positive cancers other than lung cancer or thyroid cancer were also announced at this meeting.
The details are as follows.

Research background: Selpercatinib is a highly selective and potent RET kinase inhibitor, which has been approved in many countries/regions for the treatment of RET fusion-positive lung cancer or thyroid cancer.

RET fusion is also related to the pathogenesis of other tumors.

In an international multi-center registration trial, the efficacy and safety of selpercatinib in the treatment of RET fusion-positive non-lung cancer/non-thyroid cancer patients were evaluated.

Research method: The LIBRETTO-001 study is a phase 1/2 clinical trial (NCT03157128), which included adult patients with locally advanced or metastatic RET fusion-positive non-lung cancer/non-thyroid cancer (data deadline: March 19, 2021) .

The patient received the recommended dose of 160 mg selpercatinib orally twice a day.

Patients who have been enrolled for a long time will be followed up for 6 months from the first administration, including those whose efficacy can be evaluated.

The researcher uses RECIST 1.
1 for evaluation.

The primary endpoint of this study is the objective response rate (ORR).

Secondary study endpoints include duration of remission (DoR), time to remission, and safety.

Research results: 32 cases of RET fusion-positive non-lung cancer/non-thyroid cancer include 12 special tumor types: 9 cases of pancreatic cancer; 9 cases of colon cancer; 2 cases each of breast cancer, salivary gland cancer, sarcoma and unknown primary cancer; carcinoid, Rectal neuroendocrine cancer, small bowel cancer, xanthogenous granuloma, ovarian cancer and lung cancer sarcoma were each in 1 case.

The median age is 48 years (range 22-85).

Twenty-nine patients had previously received systemic treatment (median number of treatment lines was 2, range 0-9).

ORR was 47% (N=15/32, 95% CI: 29-65).

Objective remissions were observed in 9 special cancer types (including colon cancer, pancreatic cancer, carcinoid cancer, small bowel cancer, salivary gland cancer, granulomatous sarcoma, breast cancer, ovarian cancer, and sarcoma), and another 5 patients had stable and persistent disease ≥16 weeks.

The median time to remission was 1.
9 months (range 0.
7-7.
3).

The median DoR has not been reached (median follow-up time is 13 months).

73% (11/15) of the patients are still receiving treatment.

The safety of this population is consistent with the overall safety of selpercatinib treatment.

No patient in this cohort discontinued treatment due to treatment-related adverse events (AEs).

Research conclusions: selpercatinib has shown promising anti-tumor activity in non-lung cancer/non-thyroid cancers (including a variety of refractory gastrointestinal malignancies) that are positive for RET fusion.

Multi-gene testing is essential for identifying possible cancer driver genes (including RET fusion).

The LIBRETTO-001 study will continue to explore the safety and effectiveness of selpercatinib in the treatment of these cancers.

Reference: CT011-Efficacy and safety of selpercatinib in RET fusion-positive cancers other than lung or thyroid cancers